Lyme Disease Background
Borrelia burgdorferi (Bb) is utilized herein as a generic term which encompasses several Borrelia species associated with, and believed to be, the causative agent of Lyme borreliosis (Lyme disease): B. burgdorferi sensu stricto, B. garinii, and B. afzelii, et. al. This disease is transmitted by the bite of various species of Ixodes ticks carrying the spirochete. The main reservoir of the infection in the United States is the white footed mouse, Peromyscus leucopus, and the infection can be transmitted to many mammalian species including deer, dogs, cats, and humans
The first and foremost problem with Lyme disease is accurate diagnosis. There are reasons for these difficulties in diagnosis. To start, the initial bite of an infected tick may go unnoticed by the patient, and then the clinical manifestations of Lyme disease can significantly vary among diagnosed patients. Common general symptomatology such as fever, malaise, and arthritis can resemble the symptoms caused by many other conditions, further complicating an accurate and timely diagnosis.
The second reason contributing to difficult diagnosis of Lyme disease is that the primary traditional diagnostic method currently available is limited to detecting Lyme Borrelia antibodies which, in general, is retrospective and of little use to treating patients in acute-phase states (to be explained). Complicating the immune reaction specifically is that this infective agent sometimes invades the immunoglobulins themselves, rendering detection of an immune response utilizing antibodies impossible. Further complicating testing despite the presence of an active immune response, the disease can persist for years in patients unless it is treated early. Such persistence is postulated to be the result, at least in part, of antigenic variation in the bacterial proteins. In many cases this persistence is assumed to be from repeated exposures (infective tick bites).
The accurate diagnosis of Lyme disease in humans and animals has been compromised by the lack of definitive serology (blood testing) which should lead to rapid and accurate diagnosis, but does not. The current generally accepted diagnostic tests suffer from low sensitivity and specificity, as illustrated by a recent survey of diagnostic laboratories performance issued by the Wisconsin State Laboratory of Hygiene. A simple, sensitive and specific diagnostic methodology, and a useful serologic method of testing for the early detection of Lyme disease is presently lacking but is really needed within the art to apply effective treatments.
In addition, antibiotic therapy is highly effective, especially if administered in the early stages of infection of Lyme disease, much more than late stage infections. Early and accurate diagnosis is necessary to allow this standard therapy to work. However, serious complications can result from a missed diagnoses and inappropriate treatment. Also, there is no commercially available or useable vaccine for human Lyme disease, so the development of accurate and sensitive laboratory diagnosis is an important goal of Lyme disease research as prevention is impossible. The longer the infection is in the system, the more difficult it becomes to eliminate.
Lyme Disease is the fastest growing vector borne illness in the country according to the CDC. To date, there are no consistently reliable, non-invasive and affordable testing methods. The disease is difficult to diagnose on symptoms alone due to variations in symptom patterns.
Treatment offered beyond the 7th day from the initial infection period shows more relapse responses and bacterial resistance to treatment. As time goes by, treatability becomes progressively more difficult. These spirochetes adapt to chemical (antibiotic) assault with adaptive genetic coding shifts, and maintains the information for future generations. The spirochetes are even known to have migrated to the central nervous system before the erythema migrans rash erupts.
Spirochetes will also rapidly congregate in tendons and joints, making it more and more difficult to access the pathogen for testing as it moves deeper into tissues over time. This pattern also makes it exceptionally difficult to eradicate when the Borrelia moves into these non-vascular synovial fluids and nervous tissues utilizing the treatment of blood borne antibiotic treatments.
Difficulties with proper detection remain an issue with the testing protocols presently recommended by the CDC, which has a serum only requirement, and utilizes the Western Blot and ELISA as their base standard.
The Lyme spirochete's natural mode of operation is to undergo alterations in their physical form (DNA) within the tick before transmission. The spirochetes change their genetic structure to adapt to the present carrier species as well. As it lives within a carrier, it will modulate its form utilizing the extra DNA fragments it carries to avoid immune detection. This is beyond epigenetic adaptability. These factors make it very difficult to accurately test antibodies and antigens with these variable triggers.
If the infected tick implantation is successful, it takes the tick born spirochetes 24 hours to identify this host, alter its DNA and transfer to the host mammal. After transfer, they will peak in numbers 60 days into the infection and then drop by a factor of 1000 making them almost impossible to detect there after within the blood. This is a public health issue as many people are not even aware of the tick bite and the time line associated.
Established research has shown the Borrelia organisms are present in very small numbers in the body, and are often sequestered in hard to reach places that require biopsy. Antibodies are sometimes so low or non-existent in infected individuals that they do not show positive in blood tests. Antibodies create other confusion in accurate diagnosis because they can continue to be produced, even if the infection has been eradicated.
A more difficult and impractical solution for the issue of Lyme disease will be the formulation of a vaccine to prevent this infection. The DNA structure varies and adapts to the species quickly, making it nearly impossible to create an effective human vaccine, without creating a variant of the disease or autoimmunity, which was a problem with previous attempts. Needle transmission of the isolated spirochetes creates a very different serum antibody response than a natural tick bite transmission. There is also an extremely small immune response to the spirochete alone.
Rapid treatment is the most viable and effective defense at this time. Several antibiotics work very effectively when treatment is prompt, relative to the infection onset. If there are no active Lyme Borrelia spirochetes, Lyme treatment protocols are not indicated, and alternative diagnosis procedures are indicated.
If the white blood cells themselves become infected with the spirochete, an immune response does not occur at all. Since there is tick saliva present with transmission, leukocyte (immune response) activity becomes suppressed by the saliva itself. As a result the ELISA test is quite unreliable as it is only testing certain antibodies.
The antibody schedule that typically will occur is as follows:                Week 2-4—½ of people infected will produce antibodies, only to disappear by week 8        IgM antibodies rise during the third week, peak at week 4-6 and disappear at week 8        IgG antibodies can persist for years or decades, creating false positives even if there is no active infection.        
A second bite seems to change this classic timing patterns. The peak in this case is around day 6 (according to species and organ load measured). Secondary tick bites seem to convey a certain amount of immunity and do not always stimulate a flair of immune responses or infection symptoms. Choosing and using the right antibody mediated testing procedure at the right time seems impractical.
These are significant problems impeding accurate detection of Lyme disease infection, and therefore proper treatment.
Only extremely healthy people with very healthy immune systems can produce antibodies to the tick saliva to inhibit future tick implantation, or produce tick rejection. The more immune compromised an individual is, including simple generalized stress response, the more likely it is that infection will take place, the antibiotics can fail, and there will be a relapse into so called, long-term Lyme syndromes.
The Western Blot has its own issues, as much of the test depends on antibody reactive band activity from any flagella from any form of spirochete and is not Lyme specific so it can also include all Treponema spirochetes, including those that cause syphilis, yaws and periodontal infections.
Unfortunately the Western Blot and the ELISA tests are presently the gold standard of Lyme testing in the field, primarily because they utilize blood as the testing source. The commercial labs and hospitals and so forth tend to use one antigen test, when there are many, and they are notoriously under-diagnosing Lyme disease due to this lack of consistency. False negative testing can lead the patient being up to 20 years on the wrong treatment pathway medically.
Related Lyme Borrelia Behavior Background
The scientifically established and determined normal behavior of the Lyme Borrelia spirochete is the key focus of this procedure. When there is a behavior that has a stimuli and response action, it becomes artificially manipulable. Manipulating the natural behavior of the Lyme spirochete makes it more precisely testable.
The Lyme Borrelia organism is one of the most adaptable and changeable organisms on the planet. This spirochete can rapidly change its genetic structure to adapt and respond to any environmental pressure. For example, when the spirochete is being starved by its tick host it has the extreme morphic ability to change into an encysted form within one minute of being genetically expressed in order to await a more favorable environment or host (up to ten months). They can do this as a result of possessing and utilizing the largest number of optional genetic units of replication of any bacteria known.
Though all Borrelia groups are classified as spirochete bacteria, they behave as exceptionally intelligent protozoa. Having predictable behaviors makes it possible to manipulate these spirochetes. The traditional approaches to manipulating or controlling bacteria with antibiotics or vaccines does not work as well as hoped for with these organisms as they also possess a unique flexibility in that they can rearrange their genetic structure appropriately through chemotaxis to avoid detection and create resistance. (Chemotaxis=the detection of minute changes of the chemistry of their environment). These spirochetes also have a great ability for multi-drug efflux as they become exposed to new treatment medications. (Efflux=organism develops the ability to have the killing drugs flow out of them before they can do harm). With this disease, it is uniquely important to manipulate and control these reactions to rapidly and effectively detect and treat the infection when the pathogen is vulnerable.
All Borrelia spirochetes also utilize chemotaxis for monitoring and adapting to the changing worlds it can live in. It extends survival. For example, chemotaxis is used to detect when the spirochete's host (tick) is feeding, as well as identification of what species it is feeding upon. There are 24 extra segments of DNA available for the spirochete's use at any time to adapt to a new host's environment. This is dependent upon the detection and identity of the DNA of the tick's new and future host (mammal), as detected by the spirochete through the host blood upon which the tick is feeding.
The Lyme Borrelia then will sort out which strands will be utilized, and the organisms communicate with each other to modulate the correct variations of DNA strands to ensure the greatest survival in the new host, splicing in the new variables. These DNA strands contain information on how to make changes to the Lyme Borrelia's own physiology to evade that mammal host's immune system. This Borrelia strain will hold that memory for future generations to use as well. When that configuration is internally calculated, the spirochetes triple to quadruple their population in preparation for transfer to the mammal host. As prior arts have established, 154 genes in all are altered in this process (75 are up-regulated and 79 are down-regulated). Thirty-seven changes occur in the outer protein membrane alone, as discovered thus far. These are extremely difficult parameters when considering vaccines, tests, and treatments. The variations are almost limitless.
At this stage the spirochetes are within the saliva of the tick vector. The Lyme Borrelia moves into the mammalian host through this exchange of blood and saliva. It genetically alters itself once again as a group to penetrate the epithelial tissues, creating more collagenolytic, fibrinolytic and proteolytic products beyond the activity of just the tick saliva to facilitate this process. Once cloaked in its invasive identity, the spirochetes move slowly through the blood of the mammal host, seeking collagenous and dense tissues. The Bb as all Borrelia share the same lack of preference for blood and a strong affinity for dense collagenous tissues. They move even faster in collagen than in blood. Some of the densest tissues are across the blood brain barrier. This is why within days of infection Lyme can be detected in the central nervous system of the host and in the aqueous humor of the eyes. The organism can be detected soon after that, in and around joints in the synovial fluid, evading immune and pharmaceutical attack, because it has already transferred out from the blood-rich tissues.
The solution starts with the tick's participation. When any growth stage of a tick vector starts to feed, it alternates between ingesting blood and secreting saliva into the wound it produces. The saliva is composed of a complex blend of powerful, pharmacologically active compounds, designed to bypass the host immune system and awareness as well as to prevent clotting. As soon as the new tick begins releasing this unique blend of chemicals and bio-factors into the blood stream of the mammal host with its saliva, the Lyme Borrelia in the tick begin transforming in preparation for transfer.
The genetic expression of adaptability continues once the spirochete is in the mammal's human's system. The Lyme Borrelia will adjust and adapt continuously to the individual person's body and immune system to better survive over time. The offspring are extremely well adapted to live in that particular person or organism as generations reproduce. Lyme Borrelia reproduce themselves every 8-12 hours (unlike most bacteria which is every 20 minutes). The replication period for this bacterial invasion is much slower, but more effective than other bacteria in consideration of these genetic modifications.
Lyme Borrelia will also create a defensive reaction on the genetic scale, releasing a “bleb” of DNA material to distract the host's immunoglobulin reactive system long enough for the Bb to transmute their own DNA to express differently. The sensitivity of the Lyme Borrelia spirochete allows them to detect the tiniest alterations in the surrounding environment and respond almost immediately through chemotaxic detection and genetic alteration. The same chemotaxic process is at work when the spirochete living in the host mammal detects another tick implantation.
This is the final and most relevant biological and behavioral manifestation of the spirochete. Once tick saliva factors are sensed by existing spirochetes within a tick's mammalian host, the spirochetes immediately enter the blood stream from wherever they are living and flow toward the site of the new tick attachment, attracted by the rising level of the tick saliva biofactors, as demonstrated through the pertinent research studies of Chien-Ming Shih, et al. This is the key chemically triggered behavior required to facilitate spirochete transfer to this new tick to be carried successfully to, yet a new host. Now this new tick becomes infected with Lyme Borrelia spirochetes, and the tick and spirochete duo are ready to reproduce, search for, and infect another mammal.
These events are intimately and uniquely connected to and controlled by the make-up of tick saliva factors. The full range of the effects of the hundreds of chemicals in the saliva are still being determined, as it is extremely complex. The identification of the new mammal host, the adaptation to enter the host and survive the host's immune system, the accelerated proliferation of the spirochetes, the detection of a new tick on the host, and the transfer into the new tick are all connected and mediated by tick saliva factors. The pertinent prior studies firmly demonstrated this phenomenon with mice.
The biggest problem for discovering a methodology of manipulation of this organism is that all Borrelia spirochetes are not stable in vitro (test tube), and only relatively so in vivo (living organisms). In other words, it has to be manipulated within the host in order to produce consistent results.
The collection of these established scientific observations and researches have created a knowledge base. Each avenue of research is an individual phenomenon, each as an entity unto itself. Coordinating and selective association of these data, and controlled application methodologies create a directed process for improving infection detection and treatment of Lyme disease.
The observed natural phenomena of the tick/spirochete relationships of actions and reactions create a platform of controllable variables for manipulation. Manipulation of a natural response to create an action within an unusual and predictable timeframe is essential to detect these pathogens.
Lyme spirochetes contain the largest number of genetic units of reproduction (DNA replications) of any bacteria known. They have no close relatives, genetically. The closest is the Treponema spirochete (syphilis) at 40% similar (which also can trigger a false positive with a Western Blot test). This makes active live Lyme disease very specific to detect with larger quantities of spirochetes in the blood, especially utilizing PCR diagnostic tests, if the spirochetes can be drawn directly into the blood stream.
Some of the difficulties in detecting the Lyme pathogen include the Lyme spirochete undergoing alterations in its physical form and encysting, waiting for a better time to re-activate (i.e. detection of a fresh new host). They can also rapidly change their chromosomal structure in response to environmental pressures. These organisms also change their genetic structure to adapt to the present host and their immune system. The spirochete populating adapts with differentiation from information from past infection hosts, creates a dormant or hidden infection, and the present infection can be virtually impossible to directly detect by testing blood, due to low incidence in that tissue.
Therefore, what is required is a way to manipulate Lyme Borrelia and co-infective pathogens in a controlled fashion to draw them into the blood stream, so that they are easily detected with extreme accuracy in an extraordinarily non-invasive and safe fashion. Successful manipulation of the Lyme Borrelia into the blood stream will allow for testing utilizing the PCR tests presently available, only if the serum is drawn within the time frame of diffusion toward the site of the tick saliva entry region, as demonstrated by Chen-Ming Shih, et al. in their researches demonstrating peak diffusion beginning at 24 hours and cresting at 48 hours.
In addition, drawing the Lyme Borrelia into the blood stream increases the blood concentration of the spirochetes and the lower concentrations within dense tissues connected with the use of this procedure. It is suggested that the spirochetes may also be more effectively eradicated in this phase as well. The infective agent's vulnerability at this time is the highest and will be more susceptible to traditional treatments.